The use of membranous vesicles such as liposomes and the like as adjuvants and carriers for drugs, other chemicals and biologically active compounds such as antigens and antibodies is well known in the field (U.S. Pat. Nos. 4,053,585; 4,397,846; 4,411,894; 4,427,649).
Also, many methods exist to encapsulate the various drugs or other chemicals within the vesicles. U.S. Pat. No. 4,241,046, discloses a method for encapsulating biologically active materials within liposomes by providing a combination of lipids in an organic solvent and an aqueous mixture of the material for encapsulation, emulsifying the provided mixture, removing the organic solvent, and suspending the resulting gel in water. The biologically active material is encapsulated by being processed with the liposome during preparation of the liposome.
U.S. Pat. No. 3,804,776 discloses a method for producing oil and fat encapsulated amino acids or polypeptides by dispersion. Powders of the material desired to be encapsulated are combined in a molten mixture of the lipid material. Thereafter the molten mixture is poured into water. This method of encapsulation, however, only allows for oral administration of the encapsulated material, since the droplets of lipids enclosing the encapsulted material are too large to be delivered parenterally.
Most of the other known methods also involve encapsulating the desired drug or other chemical during the synthesis of the liposome (Papahadjopoulos, et al., Biochim., Biophys. Acta, 135:639 (1967); Bangham et al., J. Mol. Biol., 12:238-252 (1965); and Bapzri and Korn, Biochim., Biophys. Acta, 298:1015 (1973)). All of the methods described, either employ laborious procedures requiring skill and training or the use of sophisticated and expensive equipment, have a low efficiency of encapsulation or low encapsulation rate or involve encapsulating the drug simultaneously with the preparation of the vesicle, thereby invoking possible leakage of the encapsulated chemical. Also these methods leave a substantial portion of the substance sequestered outside of the vesicle since at best only 50% enclosed volumes of the encapsulated material relative to total volumes of the vesicles have been reported. These methods therefore require that expensive drugs used for encapsulation be recovered from the drug solution in which the vesicles were prepared. The prior art field of encapsulation methods thus has a number of very serious problems.